TY  - EJOU
AU  - Acuña, Leonardo 
AU  - Sabagh, Mariam Ahumada 
AU  - Castillo, Víctor David Osorio 
AU  - Gooden, Caverly 
AU  - Veisaga, María Luisa 
AU  - Liuzzi, Juan 
AU  - Barbieri, Manuel A. 

TI  - Costunolide as a Conceptual Framework for Host-Directed Antiviral Modulation: Mechanistic Insights and Future Perspectives
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - Costunolide, a sesquiterpene lactone from <i>Saussurea lappa</i> Clarke, exhibits broad pharmacological properties, including anti-inflammatory and anticancer effects. This review examines its emerging potential as a host-directed antiviral compound. Costunolide modulates conserved host signaling pathways frequently exploited during viral infection, including nuclear factor-kappa B (NF-κB), the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, and mitogen-activated protein kinase (MAPK) cascades. Inhibition of NF-κB may suppress viral transcription in human immunodeficiency virus (HIV-1) infection, while NLRP3 blockade may limit inflammasome-driven viral reactivation in Epstein–Barr virus (EBV) infection and attenuate hyperinflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease. Additional modulation of phosphoinositide 3-kinase/AKT (PI3K/AKT), Janus kinase/signal transducer and activator of transcription (JAK/STAT), and Wnt/β-catenin pathways further expands its host-directed antiviral profile. These pleiotropic effects are mechanistically linked to the electrophilic α-methylene-γ-lactone moiety, which undergoes cysteine-directed Michael addition on target proteins. Collectively, these findings position costunolide as a promising host-directed antiviral scaffold, though pharmacokinetic optimization and virus-specific experimental validation remain necessary prerequisites for therapeutic translation.
KW  - Costunolide; antiviral activity; nuclear factor-kappa B pathway; NOD-like receptor family pyrin domain-containing 3 inflammasome; mitogen-activated protein kinase signaling; viral replication

DO  - 10.32604/biocell.2026.079670